Lyophilization is a process which removes solvent from a solution to form solid or powder which is stable and easier to store at elevated temperature than the liquid. Lyophilization, also known as freeze drying, involves freezing followed by sublimation. The resulting lyophilized matter may be stored without refrigeration, reducing storage and transportation costs of the substance as well as the storage space required for the product. It also can reduce the weight of the product, which similarly reduces shipping and related costs. Lyophilization is particularly useful for preserving and storing various biological molecules, because it increases their shelf-life.
Biological molecules are more difficult to stabilize via formulation than small molecules due to the number of chemical groups and dependence of stability on maintaining native folding. For this reason, many commercial biological molecules are lyophilized. In general, lyophilization improves stability through (i) the removal of water (since most biologic chemical degradations are hydrolytic) and (ii) decreasing the overall mobility of the system (since dynamic movement of side chains and molecules is necessary for chemical and physical degradation events to occur).
Lyophilized biological molecules are reconstituted prior to use, often in the very containers in which they were lyophilized and stored. Short reconstitution time is preferable for both physicians and patients. If the reconstitution time of the lyophilized biological molecule is too long, it will increase the preparation time thus making it difficult to administrate to many patients at the same. In addition, many biological molecules are designed to be administered by the patients themselves. A shorter reconstitution time ensures that patients will completely reconstitute the biological molecule before administration, thus improving safety and efficacy.
Previous efforts to reduce reconstitution time have focused primarily on the formulation of the reconstitution buffer. In contrast, the present invention is directed to the addition of a volatile additive to the formulation of the buffer used for lyophilization of a biological molecule. Thus, there is a need for methods and compositions for reducing the reconstitution time of a lyophilized biological molecule.